Therapeutic dose prediction for biologic drugs is based on pre-clinical data, including PK/PD measurements in animal models. We submit that with an advent of new complex biotherapeutic modalities, such as multi-valent or multi-specific antibodies, confident translation from pre-clinical species to humans might benefit from further characterization of potential differences between animal and human systems. Specifically, biological processes impacting PK, such as off-target binding or target mediated drug disposition (TMDD). In the proposed presentation, we suggest discussing case studies of implementing flow and imaging-flow cytometry assays with primary cells from liver and spleen, as representative organs, to evaluate propensity for TMDD and off-target engagement in humans and non-human primates (NHPs), as a major pre-clinical specie. This type of data might prove critical in improving NHP-to-human correlation, facilitating clinical success of novel drug modalities.
Learning Objectives:
Upon completion, participant will become aware of new methodologies of implementing cell-based analytical approaches to inform de-risking and human dose projection for complex biotherapeutic modalities.
